THE STAGES OF METHYLATION AND HEALING

People without any symptoms and who have no startup of methylation or anything else with the Deadlock Quartet find 800mcg of L-methylfolate quite sufficient and no need for any additional potassium by symptoms (none applicable). For me, I had hindered healing and cell formation my whole life. For me, it’s like all the tissues built during these years have to be rebuilt.

I have no idea if that is the case but that could account for that high potassium, getting rid of faulty cells built with workaround methods and replacing them with healthy cells. After I develop all those lesions in the first days of folate deficiency (however arrived at) when my folate levels return to full functionality the lesions have healthy tissue grow under them and they slough off. What happens with the equally rapidly induced IBS with the induced folate deficiencies (also injected quantites of broken down by light MeCbl (HyCbl and AquaCbl equilibrium in some percentage). Does that too from lesions that are then sloughed off by new tissues built underneath?. That happens to my angular cheilitis as well. When it starts it is like fissures opening up. When it heals it heals from underneath and sloughs off the whole damaged layer.

A current research question revolves around why so many people don’t develop IF or parietal cell antibodies until AFTER PA starts up. That of course is opposite the way that had been assumed for decades. It appears to me that autoimmune problems get triggered in the more severe methyl trap or maybe methyl trap with faulty mitochondria, not in partial methylation block. This is an unknown area so who knows.

The recent discovery of quad helix DNA in cancer cells points right at that MeCbl-l-methylfolate DNA replication point. Something goes wrong and bam! So where in the system breakdown does this happen?

Perhaps I am trapped between higher need for potassium via methylation but at the same time something going on with either my Na-K+ ATPase pumps or 11 beta HSD1 or too much glucocorticoids that is driving me to high excretion.
There ATP raises it's head. There are so many reactions dependent upon ATP. Rich said the estimate is that we use maybe twice our weight in ATP daily, made rapidly and recycled. What happens when the mitochondria are not working right? Not enough ATP for everything. The research report on the low cobalamin and increased MMA as pointing at mitochondria in the brain with AdoCbl surprised Rich and he commented on it in a posting at the time. However, even more surprising to me is how local the deficiency can be, getting enough in one part of the brain but not other parts.

I ended up introduing each thing as I saw what haden't responded, so I did get to see specfic responses to each of the items. I also think I lost valuable time and causing much worse damage to my nerves and delayed my healing by years with all the setbacks and leaving partially healed damage in weird places for lack of any number of things.

Getting started with the three vitamins of the deadlock quartet and getting mitochindria starting to recover, allows a more balanced approach without hitting into brick wall after brick wall and playing guessing games with what is missing. I don't know that trying to start methylation without starting corresponding ATP generation doesn't ending up causing so problems that wouldn't have happened otherwise. I had perhaps 25% mito startup with MeCbl, 25% with AdoCbl and 50% with LCF. If I had done the LCF before AdoCbl they would have started up 75% all at once with no effective titration control. Order can be importantt.

This was extremely helpful. I increased the potassium gluconate yesterday to about 3 grams as an experiment. This morning I woke up with my legs not aching for the first time since starting B12 injections. On general principles, I was starting to supplement with 1 gram of potassium a day, but that was not enough. I never recognized my symptoms in the list of potassium deficiency symptoms so totally missed the obvious. Thanks for making it so clear. This is a huge piece of the puzzle for me.

The other symptom that may be due to potassium is brain fog. To me it is a sense of inflammation and pressure in the brain that causes an inability to focus. That is the symptom that I get when I react badly to a supplement. The last ones were Vitamin D and magnesium. It was very interesting to read Fredd say somewhere in this thread that those were some of the common supplements to begin start up reactions for those who don’t have start up with the methyl products. Now I’m experimenting to see if potassium eradicates the brain symptoms. My first impression is that it does.

How high is it recommend to supplement with potassium before cutting down on methyl products? Doesn't potassium inhibit B12? Does potassium only inhibit absorption of B12 in the gut or does it also affect sublingual and injected B12 absorption?

Freddd, I was reading back over your first post in response to my questions about the cobalmin lettered diseases. I think in my last post asking about the distribution by diffusion I asked something you already answered back then. In effect you said that this is not the level at which you are concerned with. It is the pragmatics of what happens in practice that you are working out. So I’m sorry to have reiterated something you already addressed. Still, if anyone has any knowledge about the mechanisms of how the Methyl and Adenysol B12 could be distributed by diffusion into cells, I’d really be interested.

Blessings
Linda

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Hi Linda,

How high is it recommend to supplement with potassium before cutting down on methyl products? Doesn't potassium inhibit B12? Does potassium only inhibit absorption of B12 in the gut or does it also affect sublingual and injected B12 absorption?

In hearing of the extremes some people are going to it is clear that there is another branch in all this that handles potassium, and some other things, quite differently for reasons possibly being discussed. I'm 6 feet tall and 200 pounds, to put a little scale here. I would think that if you exceed 3000mg that it would be wise to further dig into the reasons. I find the extreme amounts likely indicative of some further co-morbidities or something. The trick is in learning to recognize each of the branchings that has multiple people exhibiting the same responses.

I trust you have seen the discussions of diffusion. After all it is well demonstrated by every injection and every sublingual.

As far as I understand it L-carnitine products can't be purchased in Canada but can be ordered in personal use quantities from the USA. I read the report causing the prohibition of l-carnitine, as much as was published any way, and saw his medications and supplements. He had an "extreme" reaction when he added l-carnitine. He was taking klonopin for anxiety and a whole lot of stuff, like a lot of us when sick. I used to carry a gadget bag full of meds, water, peanuts or crackers to eat with some meds, everywhere. It looked to me very possible that this is the type of carnitine reaction the person was having.

Freddd You can find acetyl l-carnitine and just plain l-carnitine here, but I have yet to find l-carnitine furmarate. When I ordered some from the States I held my breath until it crossed the border. I know it's legal, but it wasn't so, until a couple of years ago and if some border person is looking at outdated material, then it gets sent back and I'm out that money.

There's also something new I encountered with shipping to Canada. Apparently no more than 5 of the same item can be sent at a time. So one of my vitamin supply places wouldn't send me the 10 bottles of ENZY I ordered. They only sent 5. Last week I placed an order with iherb. I was very glad to see they've switched shipping companies so we Canadians can now track our orders. I ordered 12 bottles of ENZY and a bottle of the Anabol and held my breath. It all was delivered, in just two days, in a snow storm. Woohoo! But I just wanted to give a heads up to those Canadians ordering large quantities that they may encounter a 5 item rule.

You'll have to be quite intelligient and the giving sort. First, kudos to Fred, for all his profound efforts to better explain the active b12 protocol and to help individuals with their particular challenges in using it.

But I suspect for many of us with recurrent brain fog and limited biochemistry background a 'Stages of Methylation and Healing for Dummies' would help greatly. You wouldn't have to write a 'Dancing with Wu Li Masters'--like interpretation as done for quantum mechanics, but perhaps just give your own take of some of Fred's posts here in as simple a way possible. A different treatment of the same thing, just simplified, with perhaps an initial reference index of some of the more obscure abbreviations.

Would do it myself, but I have a full time job, a time-consuming interest that already interferes with this job, not to even mention I'm one of the dummies who needs this help in the first place.

I am curious to know how much cytomel you are taking. There are plenty of references out claiming B12 is necessary to properly use thyroid hormome. I am wondering if the opposite is also true. Does hypothyroidism lead to functional B12 deficiency? I ask because I recently made the switch off cynomel to natural dessicated thyroid (NTH) and had some observations along the way.

I have been both hyper and hypo these past few months as I adjusted my doses of cynomel and NTH. It seemed that my progress on B12/folate would plateau when I was hypo, and healing would again accelerate when I had enough thyroid hormone.

So I guess what I am wanting to know is this: Are there people out there not progressing as well or quickly with B12/folate as they would like, because they are hypothryoid?

I am curious to know how much cytomel you are taking. There are plenty of references out claiming B12 is necessary to properly use thyroid hormome. I am wondering if the opposite is also true. Does hypothyroidism lead to functional B12 deficiency? I ask because I recently made the switch off cynomel to natural dessicated thyroid (NTH) and had some observations along the way.

I have been both hyper and hypo these past few months as I adjusted my doses of cynomel and NTH. It seemed that my progress on B12/folate would plateau when I was hypo, and healing would again accelerate when I had enough thyroid hormone.

So I guess what I am wanting to know is this: Are there people out there not progressing as well or quickly with B12/folate as they would like, because they are hypothryoid?

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Hi Pela,

I've been diagnosed hypothyroid since 8 years old. It is included in the list of symptoms and signs for b12/folate. I'm working out a hopefully more meaningful arrangement of the symptoms. Hypothyroid is very common in this neighborhood. The thyroid gland has mitochondria which need AdoCbl among other things to function. Thyroid cancer cells have more mitochondria than healthy cells So the cancer cells need more b12 than healthy cells.

I also noticed how slowly any healing happened before MeCbl, months to get over a cold or strep throat. However I was on thyroid or later Synthroid or whatever, the whole time. After MeCbl almost everything worked better. And that became more and more as I added the other 4 of the Deadlock Quartet..

You'll have to be quite intelligient and the giving sort. First, kudos to Fred, for all his profound efforts to better explain the active b12 protocol and to help individuals with their particular challenges in using it.

But I suspect for many of us with recurrent brain fog and limited biochemistry background a 'Stages of Methylation and Healing for Dummies' would help greatly. You wouldn't have to write a 'Dancing with Wu Lu Masters'--like interpretation as done for quantum mechanics, but perhaps just give your own take of some of Fred's posts here in as simple a way possible. A different treatment of the same thing, just simplified, with perhaps an initial reference index of some of the more obscure abbreviations.

Would do it myself, but I have a full time job, a time-consuming interest that already interferes with this job, not to even mention I'm one of the dummies who needs this help in the first place.

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Hi Lou,

One of the problems I found along the way is that it is complicated to apply well. That is why I am trying to develop the decision trees for identifying what is going on and how to find the way through the maze. It is very specific about brands in certain cases. In another way it is simple, lots of repeated titrations trials becasue order matters when one is trying to identify what is needed, unless everything else needed for that reaction is also present, it doesn't happen. I had tried zinc several times for instance but it was only after at least the AdoCbl that the zinc made a noticable and even gangbusters difference. SAM-e responds differently depeding upon whether one has sufficient MeCbl and L-methylfolate or not, and all the basics. There are some additional parts coming that are difficult to say correctly.

For instance, potassium is one of those things most difficult to manage. In the package inserts of at least some time release potassium chloride brands (prescription) they warn of the hazzards of the time release form and say that they most only be used for those "unable to comply" with oral dosing. The complication is that for best effectiveness one must take frequent smaller doses. Serum halflife isn't long. It gets flushed out of serum into tissue by insulin (so possible complication there) or is used by everything that needs it at that moment or out the kidneys. Two big doses a day doesn't do the trick. 5 or 6 smaller doses works better. Other comorbidities can affect potassium usage and distribution. Timing makes a lot of little or big differences. Also, potassium from food reaches serum peak at plus 14 hours according to some research.

What I did was look for all the things that incrementally made improvments. Good luck.

I thought it was, too, based on what people were saying, Nathan's study, etc. but I've been on methylation supplements for going on two years now with no improvement whatsoever. I'll look at the Genetic testing forum, thanks.

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Hi Jeffrez,

You might find the reasons of lack of effecrivenss of b12 and folate useful. They are more predictive of what works than the testing.

I think saying it worked for most of the poeple who tried it is wrong as well.

You brought in a good quote though. Rich used a largely unrelated autism study and some assumptions and one measurement of glutathione to reccomend a treatment back in 1999. Experimental and mostly theoretical. And it potentially harmed several people as well. This was exactly my point. He waivered and changed his SMP based on how people felt in his latest revisions as well. In addition, he selected supplements that were readily available and affordable and that why it's called "simplified".

I am very familiar with these tests. I have been on this forum and the wrong diagnosis forum for several years. I don't think this necessarily validates the SMP, or even attempts to validate it. It is more of a diagnostic and an experimental diagnostic that will likely evolve as well. Xara's original point and my emphasis was that all of this is experimental and evolving and should be treated accordingly and everyone here is self diagnosing and treating to some degree. And everyone here should take responisibility for their self treatment. Also, the testing is largely empirical as clinical testing (not diagnostic) is difficult and expensive and the broad nature of MTHFR symptoms are hard to classify. How do you get an MCS patient, Fibro, a manic depressant, and someone with one of the other 14 "syndromes" under one clinical test?

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Hi Red,

Good to hear all is well with your wife after all the ups and downs. I tried the glutathione with 9 others because of Richs glutathione theories. They sounded good to us. Before trying any of the various supplements, I investigated them thoroughly. The ONLY one I tried that didn't fit all of my criteria was glutathione. There was a ton of research on glutathione at the biochemical level. There were a few pioneers, like Rich trying to figure out how to use it. There were a lot of people pushing it with theories I would consider incorrect (a big negative since if wrong therories lead to it, what is wrong with it) and it lacked any evidence at all of actually healing anybody. I put my forebodings aside and tired it anyway. I still carry damage from it. I certainly don't blame Rich. After reviewing everything you point out and a lot more, at the time and previous few years (I've been at this since 78 or 79) so "recent" may mean something different to me too, I decided to try it with 9 other people who were doing well but it was clear that we were still doing something wrong, that there was a "missing critical factor". Glutathione looked like the next possible "missing critical factor". I fiirst tried an expensive prepackaged form MAXGL or something like that and had some nerve pain relief . I ordered the far less expensive components and did the NAC/glutamate pair and it worked like gangbusters. NAC alone, and un-denatured whey, is enough to stimulate too much glutathione. There was no difference in effect however for those taking precursors or glutathione infusions. They all did the same thing, slightly slower or faster. All 10 of us had healing come to a halt and then reverse with symptoms bounding back. Body pain, like flu and inflamation slammed on. For the first time since I had discontinued 2400mg of ibuprofen after starting AdoCbl and 9 months after MeCbl, ibuprofen helped. Asthma came back. MCS came back. Allergies came back. In six weeks it was clear to me that i was having rapidly increasing Subacute combined degeneration damage and personality and mood changes and so was everybody else. Then we floundered around for months of continued worsening until vitamin branded Metafolin became available easily. Without the glutathione trial I would not have found paradoxical folate deficiency and the "missing critical cofactor", larger doses of l-methylfolate and in doing so identified the folate insufficiency symptoms that start and stop with L-methylfolate.

The dividing line for me is 1998, when MeCbl became generally availalble and the modern era of b12 research was able to start. Before MeCbl, BM, it was impossible to easily do a direct comparison for ourselves and took a large buget to do active b12 research trials. Then again there is another BM line about 5 years ago, Before Methylfolate. Again, direct A-B comparisons could at last be done. Now nobody has to take CyCbl, HyCbl or folic acid (even folinic acid and veggies) on faith.

I would suggest the possibility that the 2 most likely to directly cause potential damage suggestions or interpretations that happen on this board is taking glutathione in any form or precursor and calling hypokalemia "detox" or whatever and ignoring it. The most PAINFUL thing that occurs as a result of anything suggested here is the process of healing certain kings of neurological damage in my experience. There are a multitude of quite unpleasant and even approximately intolerable things that can happen that are not specifically damaging. I have put up with a lot of those things in order to heal. Of course, I don't read most of it. It's all I can do to keep up with the things in this one area.

I have a problem with the "new cell growth" theory of hypokalemia. It makes no logical sense. If this was truly the case, then we would see other people developing hypokalemia from donating blood, after having accidents, surgery or chemotherapy, and in athletes. Also, the hypokalemia isn't a startup effect. For me I lasted the entire 6 months I was on high dose methyl donors. At one point I needed 10 grams of supplemental potassium daily. That cannot be a healthy condition any way you look at it. I had severy arythmias and tachycardia on the protocol. Just felt majorly unstable.

I do not believe that more is always better when it comes to methylation and healing. I have already posted threads with studies showing problems with excess methylation, and studies showing methylation and healing effects maxing out at certain doses.

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See that more matches my clinical experiences. Why would I need 11 grams of potassium intake for six months (after already being on methylation for 15 months or so before that) and still be hypokalemic (with a lot of muscle cramps and pain), but when I back off the amount of L5mthf, remove TMG and SAMe, and lower P5p then suddenly I am ok at 60% of the amount.

Let's put it another way, a 70 kg person like me has a total body store of 3500 mEq. At 10 grams intake that is about 250 mEq. So I was having to ingest like 7-8% of my total body store? But at the same time I was excreting 250 mEq. Of course a subsequent hair analysis shows my Na / K ratio in the interstitial space is ~0.70 which is terrible. Believe me the only thing that lessened the cramps during that six months was to take potassium. But since most of it could not get into the cells (ATP pumps?) I excreted it.

So while for some people, the concept of a steady progression of cell growth and healing may imply a need for additional potassium, for others of us the need is way too high (too large a fraction of total body store) when on peak methylation.

Glutathione injections certainly messed me up. Those were in early 2010 and ironically Rich Vank while not necessarily recommending them to me via private communications was hopeful they would help. They were in fact a disaster since as I have outlined in another post on this thread I simply could not reassemble the component amino acids back into glutathione within the cell after transport across the membrane.

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HI Dbkita,

In a private phone conversation with a researcher I consider very knowledgable, the researcher said "I don't know of ANY way that glutathione can be safely used". That was after describing the N=10 trial and our results. That it can experimentatlly induce the methyl-trap in hours, and allow it to be reversed it in days if knowledgeable was a most interesting outcome. Also an experimental way to produce high MCV and SACD is an advance of sorts. And to do all that it doesn't have to penetrat the cell wall, merely circulate in serum. Consider assumptions. In school I took Experimental Design 1 and 2 and of course the statistics course to go along with them.

Have you considered scrapping the Folapro for Solgar metafolin. It made a huge difference for me.

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Can I ask a difference is which way? What symptoms improved? I have avoided the Metafolin since it has corn in (to which I have an allergy). My Mom swtiched from FolaPro to Metafolin for a couple of months and said she had less energy. I would love to hear what your experience was on switching in more detail.

That is a good question. Personally I have Occludin and Zonulin IgG antibodies that are really high due to a lifetime of undiagnosed Celiac's disease. I certainly have a leaky gut and blood brain barrier.My tight junctions are shot. So far I have not had much success healing them I fear.

Speaking of which has anyone had any success treating a leaky gut / blood brain barrier? I think the integrity of the gut and BBB is essential to health and regulation of the immune system and neurotransmitter homeostasis.

I am curious to know how much cytomel you are taking. There are plenty of references out claiming B12 is necessary to properly use thyroid hormome. I am wondering if the opposite is also true. Does hypothyroidism lead to functional B12 deficiency? I ask because I recently made the switch off cynomel to natural dessicated thyroid (NTH) and had some observations along the way.

I have been both hyper and hypo these past few months as I adjusted my doses of cynomel and NTH. It seemed that my progress on B12/folate would plateau when I was hypo, and healing would again accelerate when I had enough thyroid hormone.

So I guess what I am wanting to know is this: Are there people out there not progressing as well or quickly with B12/folate as they would like, because they are hypothryoid?

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I take 75 mcg of Cytomel currently. My free T3 and total T3 are not very good. I cannot take T4 or armour since otherwise rev T3 takes off. Been like that for years.

I have been having some improvements of late, by taking more and more of the Cytomel without food in the morning so maybe there is an absorption issue going on. Now that you mention it, the last two weeks even though I did not change methylation, I did shift another 6.25 mcg to without food (now 43 mcg without and 32 with food an hour later) and I DO feel a lot more of the positive methylation effects.

This is intriguing since for me only once starting the adb12 did a number of vitamins, etc. start having positive effects (namely B1, B5, biotin, alpha lipoic acid). Around the same time I also starting supplementing with calcium pyruvate and in the past calcium had caused odd neurological issues (fasciculations, mild tremors, skin issues) and since the adb12 that does not seem to be the case and if anything the calcium is helping my mood and sleep schedule. Odd. Initially the adb12 used to make me really tired but now it does the reverse (though maybe I still get a bit fuzzed for an hour mentally).

I suspect the Krebs cycle has been a major block in me for a long time. I need to find the time to introduce some L-carnitine fumarate.

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Hi Dbkita,

I would call that a lot of clues. B12 defciency causes lots of fasiculations. I would consider that a Krebs cycle block at least equal to the partial methylation block AND methyl-trap put together. As both cycles are mutually dependent it is a critical mutual dependency and deadlock. Without the well funtioning Krebs cycle one doesn't get a well fully functioning methylation cycle.

In a private phone conversation with a researcher I consider very knowledgable, the researcher said "I don't know of ANY way that glutathione can be safely used". That was after describing the N=10 trial and our results. That it can experimentatlly induce the methyl-trap in hours, and allow it to be reversed it in days if knowledgeable was a most interesting outcome. Also an experimental way to produce high MCV and SACD is an advance of sorts. And to do all that it doesn't have to penetrat the cell wall, merely circulate in serum. Consider assumptions. In school I took Experimental Design 1 and 2 and of course the statistics course to go along with them.

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Regardless of why negative impact of the injections, the lab results showed that by introducing ATP support in a matter of months my intracellular glutathione levels tripled having nothing to do with injections. The only other variable was a moderate increase in already high vitamin C intake and removing gluten from my diet. It is possible that improvement in ATP production had nothing to do with it and hence the GCL step was not a rate limiting step but then I have no other theory to explain how it tripled on its own in five months after a decade of being low an three years of being unbelievably low. Then again my rare autoimmune disease is maybe capable of anything

That is a good question. Personally I have Occludin and Zonulin IgG antibodies that are really high due to a lifetime of undiagnosed Celiac's disease. I certainly have a leaky gut and blood brain barrier.My tight junctions are shot. So far I have not had much success healing them I fear.

Speaking of which has anyone had any success treating a leaky gut / blood brain barrier? I think the integrity of the gut and BBB is essential to health and regulation of the immune system and neurotransmitter homeostasis.

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Hi Dbkita,

For me it was finally getting all the pieces functioning together, for my gut to heal. It wasn't until I could have my folate insufficiency taken care of 20+ days out of 30 that my gut thoroughly healed. And still, 3 days of folate insufficiency stars IBS. I've had that since early childhood occasionally, along with angular cheilitis. I think that getting inflammation near 100% under control is an important consideration. The longer I can maintain healing without interuption the better the persistancy of effects. One doctor with years of MeCbl clinical experience says it takes 5 years without a single slipup to heal the neurology and keep it healed. The things that recur rapidly are only partly healed.

Regardless of why negative impact of the injections, the lab results showed that by introducing ATP support in a matter of months my intracellular glutathione levels tripled having nothing to do with injections. The only other variable was a moderate increase in already high vitamin C intake and removing gluten from my diet. It is possible that improvement in ATP production had nothing to do with it and hence the GCL step was not a rate limiting step but then I have no other theory to explain how it tripled on its own in five months after a decade of being low an three years of being unbelievably low. Then again my rare autoimmune disease is maybe capable of anything

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Hi Dbkita,

This is why I was maintaining that it isn't necessary to take glutathione, just start the system up and let the body synthecize all it needs which it does very well. Way back in my 20s I discovered 16 grams of Vit C (Linus Pauling, bright guy) got rid of a chronic resistant UTI, streps, and so on. Now with MeCbl et al 6 grams a day is sufficient. The negative feedback system of the body uses MeCbl, AdoCbl and I would assume HyCbl, to flush excess glutathione from the body, just as MeCbl gets rid of a lot of toxins. What a lot of toxins in the body does do is destroy the active b12s and put the body into methyltrap that manifests as "detox" in the form of an induced folate deficiency symptoms without touching the folate. Works very well. Unfortunately it also flushes away cobalamins not included in HTC1,2,3.